Human trials are coming up.
With the help of a protein called IL-33, researchers from the University of Glasgow in the UK saw some incredible effects on Alzheimer’s-like symptoms in mice.
The mice in the study were bred to develop a progressive Alzheimer’s-like disease, and they were given daily injections of IL-33 to test out the protein’s impact on memory and cognitive function.
In humans, toxic amyloid plaques — sticky buildup that accumulates outside of nerve cells or neurons — is thought to trigger Alzheimer’s disease. Amazingly, the protein not only cleared out the toxic plaques in the mice, but it also prevented more from forming.
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“IL-33 is a protein produced by various cell types in the body and is particularly abundant in the central nervous system (brain and spinal cord),” study co-director Eddy Liew, from the University’s Institute of Infection, Immunity, and Inflammation, said in a media release.
“We found that injection of IL-33 into aged APP/PS1 mice rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week.”
In humans, Alzheimer’s disease usually results from a build-up of two types of “brain waste” - amyloid plaques, explained above, and neurofibrillary tangles, which are found inside of the neurons and are caused by defective tau proteins that clump into thick masses.
Researchers still don’t fully understand why Alzheimer’s disease is characterized by a build-up of amyloid plaques and neurofibrillary tangles as people age, but it appears that targeting these build-ups and clearing them out of the brain may be the way to effectively treat the disease.
The team observed that IL-33 appeared to kickstart microglia — immune cells in the brain — in mice, sending them towards the toxic plaques. Then, once the microglia located the plaques, the immune cells aggressively absorbed the build-ups with the help of neprilysin, an enzyme which is known to break down amyloid.
Not only did the process reduce the size and number of amyloid plaques in the mice, but the IL-33 injections also prevented inflammation in the brain tissue. Previous research has linked brain tissue inflammation to the growth and spread of toxic plaques and neurofibrillary tangles.
“Therefore IL-33 not only helps to clear the amyloid plaque already formed but also prevent the deposition of the plaques and tangles in the first place,” the release states.
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Although the results are certainly exciting, it’s important to note that this success was only seen with mice so far. The team is set to enter a Phase 1 clinical trial with humans to test the toxicity of IL-33 at the doses used in mice, but Liew holds back from jumping to any overly optimistic conclusions.
“Exciting as it is, there is some distance between laboratory findings and clinical applications,” he notes. “There have been enough false ‘breakthroughs’ in the medical field to caution us not to hold our breath until rigorous clinical trials have been done.”
However, he says there are “encouraging hints.”
For instance, he says previous genetic studies have revealed a link between IL-33 mutations and Alzheimer’s disease in European and Chinese populations, and further, the brain of Alzheimer’s patients contains less IL-33 than those without the disease.
For now, it’s a waiting game as the researchers begin their clinical trials with humans, but we’re excited to see how the results pan out.
The research is published in the journal Proceedings of the National Academy of Sciences.
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